Recent studies have demonstrated a link between low peak bone mass in early adulthood and osteoporosis later in life. Studies have indicated that calcium (Ca) intake and exercise patterns may be associated with bone mass and density in older children and adults, and that fluoride (F) may affect adult bone. However, few studies included younger children and none have examined the effects of F or Ca intake and genetic factors on bone mass/density in this age group. The goals of this project are to characterize biologic variation in bone development in healthy young children, and to understand how nutritional, behavioral, genetic and other factors interact to influence bone accretion in childhood, leading to attainment of peak bone mass in early adulthood. A cohort of 400 children already participating in a NIDR-funded longitudinal study of fluoride intake and dental fluorosis (NIDR RO1-DE09551) will be studied. Detailed information about daily intakes of F, Ca, Vitamin D, and other nutrients, and medical history is already available for each child since birth. We will continue to collect these data at 4 month intervals, and will collect exercise data for each child. To assess acquisition of bone mass over time, bone density measurements of the lumbar spine, hip, and whole body will be made, using dual-energy x-ray absorptiometry at age 4-5 years, and again at 7-8 years. Allelic variation of 6 bone-related genes will be determined by PCR-based assays, with whole blood DNA as template. Bivariate and multivariate analyses will be used to identify major modifiers of bone mass/density and bone accretion, and to examine potential interactions among these factors as they relate to bone acquisition. This study offers a unique opportunity to provide valuable insight into bone development in children, using a well-organized existing cohort for which extensive data are already available. Our results could serve as a basis for future recommendations regarding modifiable factors (such as nutrient intake and exercise) for enhancement of bone mass/density, and thereby may have important implications for prevention of adult-onset conditions such as osteoporosis.